1. Field of the Invention
The invention relates to the field of implantable drug delivery systems, specifically a magnetically controlled aspirating pump and a method for delivering metronomic intrathecal chemotherapy into the spinal fluid of a patient using the same.
2. Description of the Prior Art
When tumors develop inside the human body, the options for available treatment are fairly narrow. This is even more so when the tumor develops inside a vital organ such as the brain or spinal cord. Diseases such as leptomeningeal carcinomatosis that develop in or around the leptomeninges of the brain and spinal cord are notoriously difficult to treat and thus have a high mortality rate.
Leptomeningeal carcinomatosis is caused by metastatic seeding of the leptomeninges from systemic cancer, usually breast, lung, and melanoma. If left untreated, patients typically die within two months of diagnosis. Traditionally, the options for treating leptomeningeal carcinomatosis in or around the spinal cord include radiation, chemotherapy, and local intrathecal or intraventricular chemotherapy. Each of these prior methods of treating leptomeningeal carcinomatosis have had some form of success in the past, however each of them also contain various deficiencies and pitfalls that make them less than ideal when treating a patient. What is needed is a more reliable, easier, and effective process for treating leptomeningeal carcinomatosis.
Radiation is a common mode of treatment for leptomeningeal carcinomatosis. It is usually given as a fractionated dosage treatment, covering a certain field encompassing the spinal column, over a period of six weeks. Spatially localized forms of radiation, including cyberknife and gamma knife have been used with varying levels of success at focal areas of leptomeningeal enhancement. Although radiation is still widely acknowledged as the one of the most effective modes of adjunctive treatment, it suffers from the disadvantage of limited fractions and applications.
Another method used to combat brain tumors is systemic chemotherapy. Systemic chemotherapy is a viable option as an adjunct to radiation. However, it is limited in efficacy in metastatic seeding the spinal column by: 1) delivery across the blood brain/spine barrier, 2) development of drug resistance by the cancer cells, and 3) systemic side-effects from the chemotherapeutic agent. Because the blood brain/spine barrier is only partially broken down in the presence of leptomeningeal carcinomatosis, it still impairs the effective delivery and transport of systemic chemotherapy into the spinal fluid. Lastly, chemotherapy is distributed systemically throughout the entire body. Because the whole body of the patient undergoes the treatment (not just the spinal related area), undesirable side effects such as nausea, diarrhea, hair loss, and loss of appetite and energy may occur. Some of the side effects are so strong in some patients that chemotherapy is unavailable to them as a treatment and thus decrease their overall chances for survival.
In fact, even with radiation and systemic chemotherapy, the median survival of a patient with leptomeningeal carcinomatosis is currently only approximately six months.
Recently, intrathecal chemotherapy using either DepoCyt, a long acting liposomal Ara-C and produced by Enzon Pharmaceuticals of Japan, or methotrexate has been used with a mild degree of success. Most patients are treated with interval injections of chemotherapy via an Ommaya reservoir or via a lumbar puncture. Inevitably the tumor recurs despite treatment. Consequently, the patients may develop hydrocephalus, and eventually death.
The underlying hypothesis of using polypharmacy employed by the current invention is based on the premise that combination treatment is better than monotherapy. Moreover, the concept of controlling the delivery of the polypharmacy in a controlled metronomic methodology is advocated as a method of better control. Thus, a first step in administrating a cytotoxic agent is to determine the maximum tolerated dose (MTD). However, when used in traditional treatment methods, such as chemotherapy, the cytotoxic agents are delivered to the patient in a manner that allows the cytotoxic agents to be distributed more or less globally throughout the body of the patient. Relatively large doses of the drugs are required since only a small fraction of the administered dose will be present at the desired site at any given time. The remainder of the dose will be in the other parts of body. Moreover, a major problem with conventional chemotherapy is lack of specificity in targeting the cancer cell.
The use of large doses of toxic agents often leads to serious and debilitating side effects. Moreover, the global administration of drugs is often not compatible with combination therapies where a number of medicating agents are used synergistically to treat tumors or other conditions. Thus, the global administration of medicating agents to treat tumors and other such medical conditions is an inefficient and often dangerous technique that often leads to severe or debilitating side effects.
Recently, there have been some developments in the field of medical drug delivery systems. The majority of these systems have taken the form of a pump or other device that releases a variety of drugs into various positions in and around the body of a patient.
For example, many of the devices found in the prior art are much like the inventions disclosed in U.S. Pat. Nos. 6,852,104 (“Blonquist”) and 6,659,978 (“Kasuga”). Both of these inventions comprise a small tank for holding a drug regimen, a pump for pumping the drug regimen into the body of a patient, and some sort of electronic control system that allows the user to program the specific amount and at what time a certain drug regiment is to be administered. While these apparatuses may be ideal for administering certain drugs such as insulin to patients who are diabetic, they are neither designed nor suitable for directly treating leptomeningeal carcinomatosis within the brain and spinal cord of a patient.
Other prior art examples such as U.S. Pat. Nos. 5,242,406 (“Gross”) and 6,571,125 (“Thompson”) offer smaller, more convenient alternatives for administering drugs, however their reliance on maintaining a specific set of pressures and a certain amount of electrical current respectively makes them too complicated and prone to error.
U.S. Pat. Nos. 7,351,239 (“Gill”), 7,288,085 (“Olsen”), and 6,726,678 (“Nelson”) disclose a pump or reservoir that is capable of delivering medicating fluids to the brain, but requires that the pump and drug reservoir be implanted in different locations within the patient. This configuration is not only uncomfortable for the patient, but also increases the possibility of infection and unnecessarily complicates the implanting procedure. Additionally, every time the patient needs the drug reservoir refilled or the pump battery replaced, the physician must invasively re-enter the patient. Finally, none these prior methods disclose a way of measuring the value of the vascular endothelial growth factor (VEGF) so as to enable tailoring of the delivered medical agent, toxicity to meet the needs of a specific individual patient.
What is needed is a device and a method that is capable of delivering medicating agents directly to the cerebrospinal fluid (CSF) of the brain and spinal cord that is easy to operate and relatively simple to implant, while at the same time, is easy to maintain throughout the patient's treatment cycle and customize to the patient's specific needs without causing all of the negative side effects associated with previous treatment methods.